International Journal of Clinical Case Reports 2024, Vol.14, No.5, 262-275 http://medscipublisher.com/index.php/ijccr 267 Eucommia ulmoides extracts relative to other hypotensive agents. These findings provide a robust pharmacological basis for the traditional use of Eucommia ulmoides in managing hypertension. 5 In Vivo Studies 5.1 Animal models used in hypotensive research In the investigation of the hypotensive effects of Eucommia ulmoides, various animal models have been employed to elucidate its efficacy and underlying mechanisms. The most commonly used model is the spontaneously hypertensive rat (SHR), which is a well-established model for studying hypertension and its treatment. For instance, one study utilized SHRs to evaluate the antihypertensive fractions of Eucommia ulmoides Oliv., specifically focusing on lignans (EuL) and iridoids (EuI) (Luo et al., 2010). Another study also employed SHRs to assess the safety and efficacy of Eucommia ulmoides extract in reducing systolic blood pressure (Lang et al., 2005). Additionally, the hypertensive cardiac remodeling effects of lignan extracts from Eucommia ulmoides were investigated using SHRs, further demonstrating the relevance of this model in hypertension research (Li et al., 2013). The renal expression of NADPH oxidase has an essential role in the development of hypertension in spontaneously hypertensive rat via the production of superoxide, which constricts arterioles and enhances the tubuloglomerular feedback response (Welch et al., 2000). Renal NADPH oxidase is upregulated by angiotensin II , interleukin, tumor necrosis factor -1β, TNF A, and resistance of regulation of afferent and efferent arteriolar resistance have important roles in keeping the glomerular pressure constant and preventing hy pertensive glomerular damage in models of hypertension. Treatment with EU extract and its component geniposidic acid reduced NADPH oxidase and superoxide production, the blood pressure was significantly reduced (Ishimitsu et al., 2021). 5.2 Short-term and long-term effects observed The short-term and long-term effects of Eucommia ulmoides on blood pressure have been extensively studied. In short-term studies, Eucommia ulmoides lignans (EuL) were found to lower blood pressure dose-dependently in both Sprague-Dawley (SD) rats and SHRs, with significant reductions observed shortly after administration (Luo et al., 2010). Specifically, EuL was effective in reducing blood pressure when administered either intravenously or intragastrically. In another short-term study, SHRs treated with Eucommia ulmoides extract showed a reduction in systolic blood pressure beginning on day 8 of treatment, with a decline rate of approximately 10 mmHg per hour (Lang et al., 2005). Long-term studies have also demonstrated the sustained hypotensive effects of Eucommia ulmoides. For example, SHRs administered Eucommia ulmoides extract daily for 22 days exhibited a consistent reduction in systolic blood pressure (Lang et al., 2005). Furthermore, a 16-week study involving SHRs treated with lignan extracts from Eucommia ulmoides bark showed not only a reduction in blood pressure but also improvements in echocardiography examination and histomorphometry indices, indicating a preventive effect on hypertensive cardiac remodeling (Li et al., 2013). These findings suggest that Eucommia ulmoides has both immediate and prolonged benefits in managing hypertension. 5.3 Dose-response relationship and safety profile The dose-response relationship of Eucommia ulmoides has been a critical aspect of its evaluation as an antihypertensive agent. In one study, Eucommia ulmoides lignans (EuL) were administered at different doses (150 and 300 mg/kg twice a day) to SHRs, and a dose-dependent reduction in blood pressure was observed (Luo et al., 2010). The study also noted that the plasma level of nitric oxide (NO) increased, while renin activity (RA) and plasma concentration of angiotensin II (Ang II) decreased with long-term oral treatment of EuL, suggesting a mechanism involving the regulation of the renin-angiotensin system (RAS) and direct arterial relaxation. Another study explored the safety and efficacy of Eucommia ulmoides extract by administering doses of 200 mg/kg, 600 mg/kg, and 1 200 mg/kg daily to rats for 28 days. The results indicated that the extract was safe up to the maximum tolerated dose (MTD) of 1 200 mg/kg, with no evidence of acute toxicity based on clinical
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